title: CRACC-CRACC interaction between Kupffer and NK cells contributes to poly I:C/D-GalN induced hepatitis.
abstract: CD2-like receptor activating cytotoxic cells (CRACC) is known as a critical activating receptor of natural killer (NK) cells. We have previously reported that NK cells contribute to Poly I:C/D-galactosamine (D-GalN)-induced fulminant hepatitis. Since natural killer group 2, member D (NKG2D) is considered critical but not the only activating receptor for NK cells, we investigated the role of CRACC in this model. We found that CRACC was abundant on hepatic NK cells but with low expression levels on Kupffer cells under normal conditions. Expression of CRACC on NK cells and Kupffer cells was remarkably upregulated after poly I:C injection. Hepatic CRACC mRNA levels were also upregulated in Poly I:C/D-GalN-treated mice, and correlated positively with the serum alanine aminotransferase (ALT) levels. CRACC expression on Kupffer cells was specifically silenced by nano-particle encapsulated siRNA in vivo, which significantly reduced Poly I:C/D-GalN-induced liver injury. In co-culture experiments, it was further verified that silencing CRACC expression or blockade of CRACC activation by mAb reduced the production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Collectively, our findings suggest that CRACC-CRACC interaction between NK cells and resident Kupffer cells contributes to Poly I:C/D-GalN-induced fulminant hepatitis.
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Yangxi
authors.initials: Y
authors.lastname: Li
authors.forename: Guoshuai
authors.initials: G
authors.lastname: Cao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005688:Galactosamine / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011070:Poly I-C / Q000009:adverse effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D005688:Galactosamine; D011070:Poly I-C